The inability of the host to eliminate cancer cells remains a major problem. Although an increasing number of therapeutic monoclonal antibodies have been approved for treatment of various cancers, emergence of resistance to these antibodies is frequently observed, given the many different molecular pathways underlying cancer growth and progression to metastasis. Although the immune system is the principal mechanism of cancer prevention, cancer cells counteract immunosurveillance. Natural control mechanisms have been identified that limit T-cell activation so as to prevent collateral damage resulting from unrestrained T-cell activity. This process has been exploited by tumor cells to evade immune responses. Restoring the capacity of immune effector cells, especially T cells, to recognize and eliminate cancer is a major objective in immunotherapy.
The T cell Ig and ITIM domain (TIGIT) protein is an immune regulator that can block T cell immunity against cancer cells. TIGIT antagonists and other immune checkpoint antagonists interfere with (or inhibit) the activity of an immune checkpoint regulator so that, as a result of the binding to the checkpoint regulator or its ligand, signaling through the checkpoint regulator receptor is blocked or inhibited. In addition to TIGIT, other immune checkpoint regulators include the TIGIT ligands, CD112, CD155, PD-1 and its ligands, PD-L1 and PD-L2; CTLA-4 and its ligands, B7-1 and B7-2; TIM-3 and its ligand, Galectin-9; LAG-3 and its ligands, including liver sinusoidal endothelial cell lectin (LSECtin) and Galectin-3; CD122 and its CD122R ligand; B7H3, B and T lymphocyte attenuator (BTLA), and VISTA.
The need exists for improved therapeutic binding antagonists or antibodies and methods of treating cancer and chronic viral infections with such reagents. Medicines for use in such improved methods of treatment may comprise antibodies or antibody fragments that specifically bind to TIGIT, PD-1 and/or PD-L1 and reverse or partially reverse the TIGIT-, PD-1 and/or PD-L1 mediated suppression of anti-tumor or anti-viral immune responses.
In view of the limitations in the ability of a host to eliminate cancer cells, a need exists for more effective compositions and methods for cancer treatment.